Ribavirin inhibits cell proliferation and metastasis and prolongs survival in soft tissue sarcomas by downregulating both protein arginine methyltransferases 1 and 5.

Abstract

Protein arginine methyltransferases 1 and 5 (PRMT1 and PRMT5) are frequently overexpressed in diverse types of cancers and correlate with poor prognosis, thus making these enzymes potential therapeutic targets. The aim of this study was to assess and elucidate the anti-tumour effect and epigenetic regulatory mechanism of ribavirin in soft tissue sarcomas (STS). We showed that ribavirin inhibited growth and metastasis and prolonged survival in animals bearing STS cells by downregulating the mRNA and protein levels of PRMT1/PRMT5 and attenuating the accumulation of asymmetric and symmetric di-methylation of arginine (ADMA and SDMA). Furthermore, ribavirin lowered the permeability of the peritoneum in KM mice bearing S180 ascites via decreasing the level of vascular endothelial growth factor (VEGF). Ribavirin was a potent inhibitor of cell proliferation and metastasis in STS cells through downregulation of both type I PRMT1 and type II PRMT5. Ribavirin could be used to enhance the efficacy of doxorubicin in STS allograft tumour models.